5 Anthracyclines and Early Breast Cancer: The End of an Era. LAnthracyclines and Early Breast Cancer: The End of an Era? L. Gianni, Journal of Clinical Oncology 2009Anthracyclines are a mainstay of adjuvant therapy for breast cancer patients worldwide, but some research data suggest that not all patients benefit.Some of the latest studies suggest that a large majority of patients (70%–80%) might not benefit,Early Breast Cancer can be treated with less toxic but equivalent regimens.

11 “…Anthracycline cardiomyopathy is characterized by a dose-dependent progressive decrease in systolic left ventricular function often resulting in CHF. In the adult survivor, it is clinically indistinguishable from CHF due to other causes…”Journal of Clinical Oncology, Vol 25, No 25 (September 1), 2007: pp

20 The Cochrane review“Based on the currently available evidence on heart failure, we conclude that in adults with a solid tumour liposomal-encapsulated doxorubicin should be favoured over doxorubicin.”“Until more evidence becomes available on tumour response and survival in patients treated with liposomal-encapsulated doxorubicin or doxorubicin in equimolar doses, we recommend the use of a higher cumulative liposomal-encapsulated doxorubicin dose as compared to the standard cumulative doxorubicin doseVan Dalen EC et al. The Cochrane Library 2006, Issue 4

31 The role of topoisomerase II alpha and HER-2 in predicting sensitivity to anthracyclines in breast cancer patients. Oakman C, Moretti E, Galardi F, Santarpia L, Di Leo AIn the search for predictive biomarkers to refine clinical prescription of cytotoxic agents, both HER-2 and topo IIα are under exploration for their potential role in identifying individuals with early breast cancer who may benefit from anthracycline therapy.Whilst recent meta-analyses support a predictive role for HER-2 amplification, it remains unclear whether HER-2 is the critical biomarker or whether it is a surrogate marker for topo IIα alteration, a known drug target of anthracyclines.The major limitation in considering HER-2 as a single marker is heterogeneity within the subgroups of HER-2 positive and HER-2 negative disease.Cancer Treat Rev Sep 14.

42 Summing-up Anthracyclines remain a mainstay of EBC and ABC treatmentCardiovascular and leukemogen risk however is not trivial and should not be overlookedData suggest that only some subgroups may derive specific benefits from anthracyclines (although not conclusive)Available non-anthra-based regimens may help us manage uncertainty while further data accumulateM. de Laurentis, XII AIOM Milano 2009